Experiments have been performed that demonstrate an active non-specific immunosuppressive factor(s) in human cord blood and in the serum of rats transplanted with Morris hepatoma 7777. The factor appears to be concentrated in the fractions containing the highest concentration of alpha1-fetoprotein (AFP). These fractions inhibit in vitro human and rat lymphocyte cultures stimulated by phytohemagglutinin (PHA), pokeweed, and allogeneic lymphocytes. Acting on the hypothesis that AFP may be an immunoregulatory protein, in vitro and in vivo studies will be performed to determine: 1) whether the active factor is AFP or, if not, what is it?; 2) what is the mechanism(s) of action?; 3) what is the biologic significance of the material? Fractionation experiments have been designed to isolate the active factor. Dose response and kinetic studies are proposed to provide insight into the mechanism of action. Depending, in part, on the results of these studies, in vivo experiments will be performed to determine the possible biologic significance with respect to normal immunologic regulation and abnormal inhibition accompanying malignancy and other diseases.